{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Lilibeth Salvador"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-GEOD-41600"],"description":["Microarray profiling using the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays was performed to comprehensively determine global changes in transcript levels in bronchial epithelial cells following elastase treatment. Elastase caused a significant change in expression (P < 0.05, fold change 1.5) of 364 transcripts corresponding to 348 genes. Elastase affected the expression of signaling molecules including chemokines, cytokines, and receptors, as well as components of the spliceosome, transcription machinery, cell cycle and ubiquitin-mediated proteolysis. Importantly, the transcriptional response to elastase was attenuated by co-administration of 10 M-BM-5M symplostatin 5. Comparison of the global heatmap of significantly modulated transcripts indicated that symplostatin 5 potently prevented the global effects of elastase. Symplostatin 5 caused a 20M-bM-^@M-^S68 % reduction in transcript levels of elastase-inducible genes including those involved in NOD- and MAPK- signaling pathways which are relevant to inflammation. Four samples were analyzed in biological duplicates. Transcriptome profile of elastase, elastase+symplostatin 5 were compared to control."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Hybridization - The labeled RNA was further purified, fragmented and hybridized with rotation at 45 M-0C for 16 h to the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. The arrays were washed and stained using the GeneChip Hybridization Wash and Stain kit on an Affymetrix Fluidics Station 450.","Labeling - Biotinylated cRNA were prepared according to the standard Affymetrix protocol from 250 ng total RNA (GeneChip 3' IVT Express Kit).","Nucleic Acid Extraction - RNA was isolated after 3 h of treatment using the Qiagen RNEasy kit","Growth Protocol - Bronchial epithelial cells (BEAS-2B, ATCC) were grown in bronchial epithelial basal media (BEBM, Lonza) supplemented with bronchial epithelial growth factors (Lonza) under a humidified environment with 5% CO2 at 37 M-0C. All culture plates and flasks were coated with collagen before use.","Sample Processing - A total of 1.2 x 106 BEAS-2B cells were seeded in 10-cm dishes and incubated further for 24 h in supplement-free medium prior to treatment."],"figure_sub":["MIAME Score","Raw Data","Organization","Assays and Data","Processed Data","MAGE-TAB Files","Array Designs"],"data_protocol":["Image Adquisition - The chips were scanned using a GeneChip 7G Scanner.","Assay Data Transformation - ID_REF =  VALUE = Log 2 GC-RMA signal","Feature Extraction - Raw data was normalized using the Robust Multichip Analysis approach and statistical analysis was done using the Bioconductor statistical software and R program. The probe setM-bM-^@M-^Ys detection call was estimated using the Wilcoxon signed rank-based algorithm. Probe sets that are absent in all of the study samples were removed from further analyses. Differential expression analysis was performed using a linear modeling approach and the empirical Bayes statistics as implemented in the limma package of the R software. The P values obtained were controlled for multiple testing (false discovery rate) using the Benjamini-Hochberg method. P value and fold induction were calculated. Differentially expressed transcripts were ranked by P values, and P < 0.05 and fold induction >1.5 were considered at a statistically significant level. Hierarchical clustering of the data was computed on log-transformed and normalized data by using complete linkage and Pearson correlation distances. Computation and visualization was done with R packages."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"pubmed_abstract":["We discovered new structural diversity to a prevalent, yet medicinally underappreciated, cyanobacterial protease inhibitor scaffold and undertook comprehensive protease profiling to reveal potent and selective elastase inhibition. Structure-activity relationship (SAR) studies and X-ray cocrystal structure analysis allowed a detailed assessment of critical and tunable structural elements. To realize the therapeutic potential of these cyclodepsipeptides, we probed the cellular effects of a novel and representative family member, symplostatin 5 (1), which attenuated the downstream cellular effects of elastase in an epithelial lung airway model system, alleviating clinical hallmarks of chronic pulmonary diseases such as cell death, cell detachment, and inflammation. This compound attenuated the effects of elastase on receptor activation, proteolytic processing of the adhesion protein ICAM-1, NF-κB activation, and transcriptomic changes, including the expression of pro-inflammatory cytokines IL1A, IL1B, and IL8. Compound 1 exhibited activity comparable to the clinically approved elastase inhibitor sivelestat in short-term assays and demonstrated superior sustained activity in longer-term assays."],"study_type":["transcription profiling by array"],"species":["Homo sapiens"],"pubmed_title":["Potent Elastase Inhibitors from Cyanobacteria: Structural Basis and Mechanisms Mediating Cytoprotective and Anti-Inflammatory Effects in Bronchial Epithelial Cells."],"pubmed_authors":["Kanchan Taori","Jean Jakoncic","Hendrik Luesch","Salvador LA, Taori K, Biggs JS, Jakoncic J, Ostrov DA, Paul VJ, Luesch H","Valerie Paul","Jason Biggs","Lilibeth Salvador","David Ostrov"],"additional_accession":[]},"is_claimable":false,"name":"Attenuation of Global Transcript Changes Induced by Elastase with Symplostatin 5 Cotreatment","description":"Microarray profiling using the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays was performed to comprehensively determine global changes in transcript levels in bronchial epithelial cells following elastase treatment. Elastase caused a significant change in expression (P < 0.05, fold change 1.5) of 364 transcripts corresponding to 348 genes. Elastase affected the expression of signaling molecules including chemokines, cytokines, and receptors, as well as components of the spliceosome, transcription machinery, cell cycle and ubiquitin-mediated proteolysis. Importantly, the transcriptional response to elastase was attenuated by co-administration of 10 M-BM-5M symplostatin 5. Comparison of the global heatmap of significantly modulated transcripts indicated that symplostatin 5 potently prevented the global effects of elastase. Symplostatin 5 caused a 20M-bM-^@M-^S68 % reduction in transcript levels of elastase-inducible genes including those involved in NOD- and MAPK- signaling pathways which are relevant to inflammation. Four samples were analyzed in biological duplicates. Transcriptome profile of elastase, elastase+symplostatin 5 were compared to control.","dates":{"release":"2013-01-28T00:00:00Z","modification":"2023-08-25T03:29:26.11Z","creation":"2021-10-05T18:55:17Z"},"accession":"E-GEOD-41600","cross_references":{"GEO":["GSE41600"],"pubmed":["23350733"],"EFO":["EFO_0002768"],"doi":["10.1021/jm3017305"]}}